Cyr61/CCN1 overexpression induces epithelial-mesenchymal transition leading to laryngeal tumor invasion and metastasis and poor prognosis.

BACKGROUND: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamous- cell carcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT), invasion, metastasis, and prognosis. MATERIALS AND METHODS: Immunohistochemistry was used to detect the expressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases of tumor-adjacent normal tissues. Vim and E-cad were used as mesenchymal and epithelial markers, respectively, to determine the relationship between Cyr61 expression and the EMT of LSCC cells. In addition, clinical and histopathological data were combined to analyze the relationship between the positive-expression rates of Cyr61, Vim and E-cad and LSCC invasion, metastasis and prognosis. RESULTS: In LSCC tissues, Vim expression rate was significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantly lower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3 and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stages T3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, the Vim expression rate was significantly higher and the E-cad expression rate was significantly lower in the group with lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in the tumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than in stages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymph node metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61 negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group than in the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive and E-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positive groups, respectively. CONCLUSIONS: Cyr61 expression is closely associated with LSCC invasion and lymph node metastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasis and poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasis and a new target for LSCC treatment.

[Anti-tumor peptide of tumstatin in the treatment of the transplantable model of human laryngeal squamous carcinoma in nude mice].

OBJECTIVE: To study the effect of anti-tumor peptide of tumstatin on tumor growth of human laryngeal squamous carcinoma in nude mice and the underlying mechanism. METHOD: Nude mice model bearing laryngocarcinoma were established by using human laryngeal squamous carcinoma cell line (Hep-II). The animals were given tumstatin or PBS for 10 consecutive days. The volumes of the subcutaneous tumor were observed. The microstructure in which the general 2-step immunohistochemical examination was adopted and ultra-micro-structural changes of carcinoma after administration of tumstatin were observed under light and electron microscopes for pathology examination. RESULT: The differences was statistically significant in the net mice weight, tumor weight, tumor volume and tumor weight/net mice weight between the treatment group and the control group (P<0.01). The restrained percentage of tumor was 51.58%. The necrosis and apoptosis of the tumor cells and the angiogenesis reduction were found under light and electron microscope in the treatment group. MVD of the treatment group was lower than that of the control group (P<0.01). CONCLUSION: Tumstatin can significantly restrain the development of laryngocarcinoma.

Bergman cyclization in polymer chemistry and material science.

Bergman cyclization of enediynes, regarded as a promising strategy for anticancer drugs, now finds its own niche in the area of polymer chemistry and material science. The highly reactive aromatic diradicals generated from Bergman cyclization can undergo polymerization acting as either monomers or initiators of other vinyl monomers. The former, namely homopolymerization, leads to polyphenylenes and polynaphthalenes with excellent thermal stability, good solubility, and processability. The many remarkable properties of these aromatic polymers have further endowed them to be manufactured into carbon-rich materials, e.g., glassy carbons and carbon nanotubes. Whereas used as initiators, enediynes provide a novel resource for high molecular weight polymers with narrow polydispersities. The aromatic diradicals are also useful for introducing oligomers or polymers onto pristine carbonous nanomaterials, such as carbon nano-onions and carbon nanotubes, to improve their dispersibility in organic solvents and polymer solutions.

Down-regulation of cyclin D1 by small interfering RNA inhibits cell growth and induces apoptosis of laryngeal squamous cell carcinoma.

OBJECTIVE: The objective of the study was to explore the inhibitive role of cyclin D1 gene silence in laryngeal squamous cell carcinoma by lentivirus-mediated RNA interference. MATERIALS AND METHODS: Cd1-RNAi-Lentivirus and the control lentivirus (GFP-Lentivirus) were transfected into Hep-2 cells. Reverse transcriptase polymerase chain reaction was performed to explore the cyclin D1 expression level in Cd1-RNAi-Lentivirus-transfected Hep 2 cells. The apoptosis and viability of Cd1-RNAi-Lentivirus-treated Hep-2 cells were measured with flow cytometry and methyl thiazolyl tetrazoliym assay. In an animal experiment, 10 mice bearing Hep-2 cell tumor were intratumorally injected with Cd1-RNAi-Lentivirus; and the other 10 mice were injected with GFP-Lentivirus. Terminal deoxytransferase-mediated dUTP nick end labeling stains and transmission electron microscope were used to observe the apoptosis in the xenografts. RESULTS: Cyclin D1 was knocked down after Cd1-RNAi-Lentivirus was transfected into Hep-2 cells. The proliferative ability of Hep-2 cells was significantly inhibited by Cd1-RNAi-Lentivirus, and a significant apoptosis of Hep-2 cells was also observed after Cd1-RNAi-Lentivirus transfection. The average weight and volume of tumors in the Cd1-RNAi-Lentivirus-treated group were significantly lower than those in the control group (P < .01). The significant apoptosis was detected with terminal deoxytransferase-mediated dUTP nick end labeling stain and transmission electron microscope. CONCLUSIONS: The present findings suggest that cyclin D1 gene silence by lentivirus-mediated RNA interference can inhibit growth and promote apoptosis of laryngeal squamous cell carcinoma.

[Inhibiting effects of TFPI-2 recombinant adenovirus on invasion of laryngeal squamous carcinoma].

OBJECTIVE: To study the effects of adenovirus-mediated tissue factor pathway inhibitor-2 gene on the invasion of laryngeal squamous cancer. METHOD: Ad-TFPI-2 was transfected into laryngeal squamous cancer (Hep-2) cell. Western-blot was used to test the TFPI-2 protein expression and Boyden Chamber experiment was used to examine the invasive ability of Hep-2 cells. Furthermore, the Ad-TFPI-2 infected Hep-2 cells were subcutaneously inoculated in nude mice and the tumor formation capability were observed. RESULT: Ad-TFPI-2 was identified correctly by endonuclease and sequencing and the virus titer was 2.8 x 10(13) PFU/L. In the Hep-2 cells of treated group, the TFPI-2 protein expression was increased while the invasive capability was descent. The tumor formation capability was also decreased in the treated group nude mouse model. CONCLUSION: TFPI-2 recombinant adenovirus can effectively inhibit the invasive capability of laryngeal squamous cancer.

[Expression of alpha-v integrin subunit in the laryngeal and hypopharyngeal squamous cell carcinomas and its relationship with tumor angiogenesis].

OBJECTIVE: To investigate the expression of integrin alpha-v subunit in laryngeal and hypopharyngeal squamous cell carcinomas (LHSCC) and to correlate the expression ratio with clinic and pathologic features of LHSCC, meanwhile, to investigate the relationship between the expression of integrin alpha-v subunit and tumor angiogenesis. METHODS: A tissue microarray of LHSCC was designed and made. Using this microarray, the expression of integrin alpha-v subunit in LHSCC was studied by immunohistochemistry, and the expression disparity in different clinic and pathologic staging of LHSCC was analyzed. The immunohistochemical staining of CD105 was done in the same microarray, the intratumor microvessel density (IMVD) was calculated by CD105 staining. The relationship between integrin alpha-v subunit expression and the IMVD was analyzed. RESULTS: In primary cancer tissue, the expression ratio of integrin alpha-v subunit was 68.0% (51/75), significantly higher than normal tissue beside cancer (10.3%, 3/29, chi2 = 28.68, P < 0.001); the expression ratio of integrin alpha-v subunit in lymph node metastatic carcinoma was 100.00% (20/20), significantly higher than normal tissue (chi2 = 38.77, P < 0.001) and primary cancer tissue (chi2 = 12.69, P < 0.05); in group with lymph node metastasis, the expression ratio of integrin alpha-v subunit was significantly higher than group without lymph node metastasis (chi2 = 10.87, P < 0.001); the IMVD of the group with integrin alpha-v subunit positive expression was significantly higher than the group with integrin alpha-v subunit negative expression (P < 0.001). CONCLUSIONS: There was significant relationship between integrin alpha-v subunit expression and lymphatic metastasis of LHSCC. Overexpression of the integrin alpha-v subunit may have contributed to the tumor angiogenesis and lead to lymphatic metastasis. Integrin alpha-v subunit may become a novel lymphatic metastasis marker of LHSCC.

[Prediction and management about perilymph gusher in cochlear implantation].

OBJECTIVE: To discuss the clinical experience of prediction and management about perilymph gusher in cochlear implantation. METHOD: Among 327 cases of cochlear implant, eleven recipients were selected by the high resolution computed tomography (HRCT) findings of cochlear malformations and bony fistula on fundus of the internal auditory canal that caused an abnormal connection between subarachnoid and perilymphatic spaces. RESULT: Perilymph gusher was found in all of these 11 recipients during cochlear implantation and was controlled with muscle tissue seal. CONCLUSION: The reason of perilymph gushers in cochlear implantation is that abnormal connection between subarachnoid and internal auditory canal. HRCT can be used to assess the possibility of perilymph gusher in surgery. The safe and rapid surgical method of gusher controlling can avoid complication.

[Review of cochlear implantation in 110 cases].

OBJECTIVE: To summarize the operation experiences in cochlear implantation. METHOD: Multiple channel electrodes were implanted in 110 patients with severe hearing loss or total deaf. RESULT: One hundred percentage of successful implantation was achieved, and the average hearing level of tone stimulation is 37.6 dB SPL. CONCLUSION: Careful examination in audiology and imagiology pre-operation is very important in achieving the successful operation with the best hearing rehabilitation results.

[First stage speech reconstruction after total laryngectomy with the improved trachea-pharynx anastomosis].

OBJECTIVE: To investigate the improved methods of first stage speech reconstruction after total laryngectomy. METHOD: We improved the method of the first stage speech reconstruction after total laryngectomy with a low level tracheotomy, reconstruction of the glottis with the ahead mucous membrane of esophagus, making stoma at the incision of trachea, lifting and shrinking the cervical trachea and sewing up to the root of tongue. This novel method was adoptioned on 35 patients, the curative effect had been observed. RESULT: Among the 35 patients, 33 patients (94.29%) regained the phonation function to a different extent. Only 2 patients (5.71%) could not speak. Most patients got an articulate and fluent voice. All of the patients could take food by mouth without severe miss deglutition. CONCLUSION: There are many excellences in our operation style. The success rate of the speech is higher, the quality of the speech is better and the rate of the miss deglutition is lower than the classical operation style of the speech reconstruction. It has no use for a factitious speech device and deserves to spread.

[Pre-operation evaluation and intra-operation management of cochlear implantation].

OBJECTIVE: To summarize pre-operation evaluation experiences in cochlear implantation. METHODS: Performing auditory evaluation and image analysis seriously in 158 severe hearing loss or total deaf cases before cochlear implantation, comparing their performance with the findings during and post operation. RESULTS: Among the total 158 cases, 116 cases with normal structure, 42 cases with the abnormal findings of the inner or middle ear. Stapedial gusher happened in 6 cases, 1 case was not predicted before operation. Except 1 case with serious malformation, the findings of other 157 cases in operation were consistent with the pre-operation evaluation. We helped all patients reconstruct auditory conduction with cochlear implantation, and the average hearing level up to 37.6 dB SPL. CONCLUSIONS: Performing image analysis seriously before operation and planning for operation according to HRCT can do great help to cochlear implantation. The operation under the HRCT instruction has less complications.